The long-term goal of our research is to prevent sight loss due to diabetic eye disease by identifying functional measures that occur early in diabetes and predict diabetes eye complications. Diabetic eye complications are the leading cause of blindness among working age adults aged 20-74 in the US. Among people with Type 2 diabetes, 90% of cases of diabetes, the leading cause of sight loss are diabetic macular, accumulation of fluid in the retina. Current treatments of edema are aimed at slowing progression and are applied after considerable retinal damage and loss of vision have occurred. These treatments, mainly laser treatments, focus on slowing acuity loss or saving central vision (acuity). Newer anti-VEGF treatments do improve acuity, but again, this treatment is applied after sight loss and structural damage. Clinical trials aimed at prevention or early treatment will rely heavily on developing means of identifying patients and retinal locations at risk for retinal edema. We have shown that the multifocal electroretinogram (mfERG) quickly and objectively evaluates retinal neural function at 103 separate retinal locations simultaneously. The measure of mfERG timing has been used in our models that predict new retinopathic signs in eyes with or without previous retinopathy. Most recently, we have turned our attention to developing a predictive model of diabetic macular edema onset. A preliminary model predictive of macular edema, which has fairly good sensitivity and specificity, uses the mfERG, which is predominantly a post-receptoral cone system response, as the sole functional measure of the eye. However, we will now develop a model that also includes measures of rod and cone photoreceptor (PR) function and retinal pigment epithelial (RPE) function, both of which are known to be affected by diabetes. Further, the RPE is responsible for pumping fluid out of the retina. Therefore functional deficits in the RPE contribute to macular edema. Its function is measured non-invasively using the electro-oculogram (EOG). The RPE is also essential for the integrity and function of the rods and cones. The full field flash electroretinogram (ERG) provides a measure of rod and cone function. Thus, the new model will include these measures of RPE and PR function. These are issues that are implicated in (RPE) or affected by (PR) macular edema. mfERGs, which is the only objective method that can identify functional abnormalities at specific retinal locations, will also be included. The ability to predict where diabetic macular edema will develop (specific retinal locations) and in which patients'eyes will provide clinicians with powerful management tools for new treatments yet to be developed. More immediately, from a research perspective, the ability to identify 'at risk'populations will greatly streamline clinical trials by reducing the number of subjects required and reducing the study period needed to establish meaningful results. This will make possible cost savings and the ability to more quickly bring new candidate treatments or interventions to the clinic. PUBLIC HEALTH RELEVANCE: Diabetic macular edema is the major cause of sight loss in people with Type 2 Diabetes, which has been called an epidemic. This project will develop a statistical model, using measures of function of the retinal pigment epithelium and photoreceptors and known health risk factors that is strongly predictive of future development of diabetic macular edema. This will enable researchers, clinicians and those who conduct clinical trials to more efficiently identify the at risk population.